JMIR Publications

ABSTRACT

Background:

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide and continues to have poor survival outcomes, with most patients being diagnosed at advanced stages of disease. In New Zealand, NSCLC contributes substantially to cancer inequities, with Māori communities experiencing disproportionately high incidence and mortality rates. Although low-dose computed tomography screening can improve early detection, major limitations remain, including false-positive findings, overdiagnosis, high infrastructure costs, and limited accessibility for rural and underserved populations. Liquid biopsy approaches using circulating tumour DNA (ctDNA), particularly DNA methylation profiling, have emerged as promising, minimally invasive strategies for improving cancer detection, treatment monitoring, and precision oncology.

Objective:

This study aims to establish integrated genomic and epigenomic predictive and prognostic biomarkers using circulating tumour DNA, tumour tissue, and transcriptomic profiling to improve early detection, risk stratification, treatment selection and response prediction, and longitudinal monitoring, with particular emphasis on identifying molecular mechanisms associated with treatment resistance and disease progression.

Methods:

This prospective observational translational biomarker study is being conducted through the University of Otago and associated respiratory and oncology services in New Zealand. The study will recruit participants with NSCLC (squamous and non-squamous subtypes), individuals referred to fast-track lung nodule assessment clinics, and non-malignant respiratory controls. Serial peripheral blood sampling will be performed in selected participants at predefined clinical follow-up time points to evaluate treatment response and disease progression. Availability of formalin-fixed paraffin-embedded archival tissues was collected but was not mandatory for enrolment. Genome-scale DNA methylation profiling will be performed using cell-free reduced representation bisulfite sequencing (cfRRBS), while targeted genomic profiling and transcriptomic analyses will be conducted using targeted sequencing panels and RNA sequencing. Integrative bioinformatic analyses will be used to identify molecular biomarkers associated with early

Results:

Ethics approval for the study has been obtained from the New Zealand Health and Disability Ethics Committee (2022 EXP 12566). Recruitment and biospecimen collection are ongoing. The study aims to recruit approximately 400 participants, including NSCLC patients, individuals referred through respiratory diagnostic pathways, and non-malignant controls.

Conclusions:

This study will generate one of the first integrated genomic, epigenomic, and transcriptomic liquid biopsy datasets for NSCLC in New Zealand. The findings are expected to support the development of sensitive, accessible, and equitable blood-based biomarkers for NSCLC detection and treatment monitoring, while also contributing to improved precision oncology approaches and reducing NSCLC inequities in Māori populations. Clinical Trial: This is an observational study and not a clinical trial. The ethics application is approved by the Health and Disability Ethics Committee (HDEC) in New Zealand. ID: 2022 EXP 12566